The trabecular meshwork of the eye is a principal site of outflow resistance to the aqueous humor. The trabecular meshwork is subjected to changes in intraocular pressure, and these could cause the trabecular meshwork cell to stretch. In an effort to determine how mechanical stretch could influence the trabecular meshwork cells, cultures of human trabecular meshwork cells were grown on silicone sheets. The sheets were then stretched by 10 percent, and the cells were followed over time. When stretch occurs, there is a very rapid loss of phosphorylated tyrosine in several proteins. One of the most prominent is a 41 kilodalton protein, which does not regain normal levels of phosphotyrosine until 1 hour after stretch. In contrast to this protein, one of the signal adaptor proteins in the cellular regulatory signal transduction pathway, Shc, is phosphorylated on a tyrosine within 2 minutes. The level of phosphorylation of Shc decreases until it returns to baseline after about 2 hours. Physically, the cells are stretched immediately and return to a less elongated morphology within about 2 hours. From the data obtained, it would appear that the human trabecular meshwork cells attempt to maintain the focal contacts to the silicone sheet immediately after stretch. These contacts are probably rearranged over the period of the next several hours to adjust to the new surface. Currently, our efforts are directed to showing that the signal transduction pathway involving MAP kinase is involved when cells are mechanically stretched. This pathway influences the transcription of the cells and may alter the types of proteins that the cells subsequently synthesize. Our hypothesis is that this alteration is different between normal eyes and eyes from individuals with glaucoma.